Captopril



Better Known as: Capoten

 * Marketed By: Bristol-Myers Squibb


 * Major Indication: Hypertension & Congestive Heart Failure


 * Drug Class: ACE Inhibitor
 * Date of FDA Approval (Patent Expiration): 1981 (1996)


 * 2009 Sales: N/A
 * Importance: It was the first Angiotensin-Converting Enzyme Inhibitor. Was one of the earliest successes of Structure-Based drug design paving the way for future discoveries.
 * See Pharmaceutical Drugs for more information about other drugs and diseases

Mechanism of Action
Extensive research has validated a pathological role for Angiotensin II in cardiac, renal and vascular diseases. Bradykinin, a small peptide that counterbalance the effects of Angiotensin II by acting as a strong vasodilator upon binding AT2, is degraded by the same ACE-1 enzyme. Since ACE-1 is the primary producer of Angiotensin II and primary degrader of Bradykinins, inhibition of ACE-1 has proven an effective treatment for Hypertension and Congestive Heart Failure. Captopril binds to the ACE-1 binding site of Angiotensin-Converting enzyme, preventing ACE-1 from binding angiotensin. Captopril, binds ACE-1 precisely, forming electrostatic interactions with His 353, Glu 384, Lys 511, His 513 and Tyr 520, along with zinc cation.